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Protein / target

Glial cell line-derived neurotrophic factor

Encoded byGDNFP39905Homo sapiensSwiss-Prot
UniProt: P39905Ensembl: ENSG00000168621HGNC: HGNC:4232NCBI Gene: 2668
Small-molecule tractable
Druggability
Structure with Ligand
2
Research papers

Protein at a glance

Biological role

Glial cell-derived neurotrophic factor receptor binding

Strongest disease association

Schizophrenia

Via encoding gene GDNF · Genetic evidence · score 0.69

Research activity

Emerging research

2 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.

View complete UniProt function annotation

Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake (PubMed:8493557). Acts by binding to its coreceptor, GFRA1, leading to autophosphorylation and activation of the RET receptor (PubMed:10829012, PubMed:25242331, PubMed:31535977). Involved in the development of the neural crest (PubMed:15242795)

Subcellular location

Secreted
Domains and Gene Ontology detail (43)

Gene Ontology

  • Cextracellular region
  • Cextracellular space
  • CGolgi apparatus
  • Fchemoattractant activity involved in axon guidance
  • Fglial cell-derived neurotrophic factor receptor binding
  • Fgrowth factor activity
  • Fprotein homodimerization activity
  • Freceptor tyrosine kinase binding
  • Fsignaling receptor binding
  • Padult locomotory behavior
  • Pbranching involved in ureteric bud morphogenesis
  • Pcommissural neuron axon guidance

211 aa · 24 kDa · 5 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationGOSynaptic signallingGOCell proliferation & survivalGOImmune signallingGOTranscriptional regulationGOApoptosis & cell deathGO
View supporting evidence

Cell migration

  • ·neural crest cell migration
  • ·neural crest cell migration involved in autonomic nervous system development

Synaptic signalling

  • ·regulation of dopamine uptake involved in synaptic transmission

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Immune signalling

  • ·neural crest cell migration
  • ·neural crest cell migration involved in autonomic nervous system development

Transcriptional regulation

  • ·positive regulation of transcription by RNA polymerase II
  • ·regulation of gene expression

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of neuron apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GDNF

Gene-level evidence surfaced through the gene GDNFthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Schizophrenia
0.73Moderately supported

Genetic evidence dominant · Open Targets 0.44

Hirschsprung disease
0.61Moderately supported

Genetic evidence dominant · Open Targets 0.35

Prostate carcinoma
0.59Moderately supported

Genetic evidence dominant · Open Targets 0.35

Obesity disorder
0.57Moderately supported

Genetic evidence dominant · Open Targets 0.34

Anorexia Nervosa
0.55Moderately supported

Genetic evidence dominant · Open Targets 0.33

View evidence synthesis (5)
SchizophreniaModerately supported
0.73
agreement 0.59–0.87
Genetic85%Literature16%

Open Targets aggregate 0.44 · 2 independent evidence families

Hirschsprung diseaseModerately supported
0.61
agreement 0.49–0.73
Genetic60%Animal model32%Literature8%Genetic literaturedup

Open Targets aggregate 0.35 · 3 independent evidence families · 1 not counted as duplicate

Prostate carcinomaModerately supported
0.59
agreement 0.46–0.73
Genetic85%Literature15%

Open Targets aggregate 0.35 · 2 independent evidence families

Obesity disorderModerately supported
0.57
agreement 0.43–0.70
Genetic94%Literature6%

Open Targets aggregate 0.34 · 2 independent evidence families

Anorexia NervosaModerately supported
0.55
agreement 0.43–0.67
Genetic100%

Open Targets aggregate 0.33 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Schizophrenia0.44
Prostate carcinoma0.35
Hirschsprung disease0.35
Obesity disorder0.34
Anorexia Nervosa0.33
Diabetes, Gestational0.33
Liver Diseases0.31

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
SM · Structure with LigandAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMM

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling.15 cites

Rangel-Sosa MM · Glia · 2024

Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly.7 cites

Houghton FM · Nature communications · 2023

Recent

Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling.

Rangel-Sosa MM · Glia · 2024

Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly.

Houghton FM · Nature communications · 2023

Europe PMC papers linked directly to this protein.